Magnetic Resonance Imaging Confirmed Olfactory Bulb Reduction in Long COVID-19: Literature Review and Case Series

Abstract

An altered sense of smell and taste was recognized as one of the most characteristic symptoms of coronavirus infection disease (COVID-19). Despite most patients experiencing a complete functional resolution, there is a 21.3% prevalence of persistent alteration at 12 months after infection. To date, magnetic resonance imaging (MRI) findings in these patients have been variable and not clearly defined. We aimed to clarify radiological alterations of olfactory pathways in patients with long COVID-19 characterized by olfactory dysfunction. A comprehensive review of the English literature was performed by analyzing relevant papers about this topic. A case series was presented: all patients underwent complete otorhinolaryngology evaluation including the Sniffin’ Sticks battery test. A previous diagnosis of SARS-CoV-2 infection was confirmed by positive swabs. The MRIs were acquired using a 3.0T MR scanner with a standardized protocol for olfactory tract analysis. Images were first analysed by a dedicated neuroradiologist and subsequently reviewed and compared with the previous available MRIs. The review of the literature retrieved 25 studies; most cases of olfactory dysfunction more than 3 months after SARS-CoV-2 infection showed olfactory bulb (OB) reduction. Patients in the personal case series had asymmetry and a reduction in the volume of the OB. This evidence was strengthened by the comparison with a previous MRI, where the OBs were normal. The results preliminarily confirmed OB reduction in cases of long COVID-19 with an altered sense of smell. Further studies are needed to clarify the epidemiology, pathophysiology and prognosis.

Association between olfactory dysfunction and mood disturbances with objective and subjective cognitive deficits in long-COVID

“…The release of pro-inflammatory cytokines and the activation of microglia reduce adult hippocampal neurogenesis, which, in turn, causes mood and cognitive disturbances typically observed in chronic inflammatory disorders ( Chesnokova et al, 2016 ). Damage to the olfactory bulb was demonstrated in long-COVID patients associated with long-term olfactory dysfunction ( Frosolini et al, 2022 ). This damage might extend to proximal and connected regions, affecting the limbic system and, consequently, impairing emotional and memory networks ( Díez-Cirarda et al, 2022 ; Goehringer et al, 2022 ; Kay, 2022 ; Martini et al, 2022 ).…”

Anosmia in COVID-19 could be associated with long-term deficits in the consolidation of procedural and verbal declarative memories

“…SARS-CoV-2 causes olfactory dysfunction in many patients, being reported by long-COVID patients as a frequent symptom (Doty, 2022). Some possible causes of olfactory dysfunction are olfactory cleft obstruction, olfactory bulb atrophy, inflammation, downregulation of olfactory receptor proteins, and massive activation of macrophages and release of cytokines (Keshavarz et al, 2021;Xydakis et al, 2021;Frosolini et al, 2022). The virus can enter the olfactory bulbs and affect the brain through transcribriform or vascular routes (Brann et al, 2020).…”

Exploratory Study on Chemosensory Event-Related Potentials in Long COVID-19 and Mild Cognitive Impairment: A Common Pathway?

“…This post-viral OD covers 40% of cases; in fact, the loss of olfactory abilities is certainly one of the symptoms that is most frequently found in affected subjects (about 87% of patients who develop COVID-19 in mild or moderate symptomatology), much higher numbers than the previous coronaviruses, which instead counted a few patients with the same dysfunction [ 56 ]. In addition, magnetic resonance studies conducted on affected and anosmic patients have reported changes in the olfactory bulb and in the structures responsible for olfactory perception [ 11 ].…”

“…Moreover, magnetic resonance imaging performed before and after COVID-19 infection has shown significant changes in experimental subjects’ brain structure compared to controls [ 10 ]. In particular, it seems that COVID-19 can cause a reduction in gray matter thickness in the orbitofrontal cortex and the parahippocampal gyrus and increased injury signs in brain areas that are functionally related to the primary olfactory cortex [ 11 ].…”